An autopsied case of Sjogren's syndrome with massive necrotic and demyelinating lesions of the cerebellar white matter

A 69-year-old woman developed subacute cerebellar ataxia and tremors in all four limbs in April 1996. Laboratory examination showed elevated antibodies against Ro and La. Head magnetic resonance imaging showed T(2) high-intensity lesions in the cerebellar white matter bilaterally and later in the pons. In April 2000, she died of multiple organ failure with incidental colon cancer. The autopsy showed atrophic parotid glands with an accumulation of lymphocytes around the ducts, confirming the diagnosis of Sjogren's syndrome histopathologically. The neuropathological examination revealed severe necrotic lesions in the cerebellar white matter bilaterally with several foci of perivenous demyelination in the periphery of the lesions and similar demyelinated areas in the pons. Immunohistochemistry with anti-JC virus antibody demonstrated no positive inclusions. A single focus of granulomatous arteritis was observed in one subarachnoid artery. The combination of Sjogren's syndrome, granulomatous angitis, and foci of perivenous demyelination suggests that an autoimmune mechanism played an important role in causing the necrotic lesions in the cerebellar white matter in this case.     

Disseminated perivenous necrotizing encephalomyelitis in systemic lupus erythematosus: report of an autopsy case

The patient, a 22-year-old woman who had been treated for systemic lupus erythematosus (SLE) for 10 years, was hospitalized for arthralgia, melena, and difficulty in walking. CT examination of the brain showed grain-like high-density lesions scattered throughout the cerebral white matter and basal ganglia. At autopsy, multiple perivenous, well-demarcated foci of brownish discoloration were seen scattered throughout the cerebral white matter and basal ganglia. Histopathologically these lesions consisted of foci of coagulation necrosis surrounding the veins. The veins in the foci showed fibrous thickening of the walls, but there were no indications of vasculitis. At the periphery of the lesions, the axons were better preserved than their myelin sheaths. The neuropathological findings in the present case closely resemble those of acute disseminated (perivenous) encephalomyelitis, although an inflammatory cell infiltration had apparently already subsided. Although its pathogenesis remains unclear, this finding should not be regarded as an incidental complication but rather as a rare subtype of central nervous system lesion occurring with SLE. Received: 18 July 1997 / Revised: 26 September 1997 / Accepted: 1 October 1997     

THE RELATION OF RETINAL PERIPHLEBITIS TO MULTIPLE SCLEROSIS AND OTHER NEUROLOGICAL DISORDERS

Two clinically different types of eye disease are often referred to as "retinal periphlebitis". Very mild perivenous changes are found in one type. These changes never lead to hemorrhages. A relationship to multiple sclerosis has repeatedly been observed. Hemorrhages and severe complications are typically found in another type. This ocular disease is sometimes associated with symptoms strongly suggesting a vascular disease in the spinal cord. Three cases with moderately severe "retinal periphlebitis" are reported in the present paper; the relation of their neurological disease to multiple sclerosis is discussed.     

A long-term follow-up of 29 cases of benign epilepsy in childhood with central-temporal electroencephalographic foci

29 cases of benign epilepsy in childhood with central-temporal EEG foci (BECCT) were followed up from 2 to 9 years clinically and electro encephalographically. Focal discharges in several cases were found to be changeable from one cerebral hemisphere to another. The subsidence of clinical seizures usually preceded epileptic discharges. Such focal discharges often disappeared before puberty whereas the clinical seizures would not manifest themselves even earlier. Small doses of antiepileptic drugs were effective for the majority of such patients. One patient with occasional seizures but without medication had been observed.     

Central nervous system immune reconstitution disease in acquired immunodeficiency syndrome patients receiving highly active antiretroviral treatment

Highly active antiretroviral therapy (HAART)-induced immune restoration has been very beneficial for acquired immunodeficiency syndrome (AIDS) patients. In rare instances, HAART may induce a paradoxical clinical deterioration due to an immune reconstitution inflammatory syndrome (IRIS). This syndrome has been described with a wide variety of systemic infections and, in the central nervous system, with Cryptococcus neoformans infection, cytomegalovirus retinitis, and progressive multifocal leukoencephalopathy (PML). The authors have examined brain tissue in eight cases of IRIS: two autopsy cases and three biopsy cases of HIV encephalitis with IRIS and one autopsy case and two biopsy cases of PML with IRIS. All the patients presented with clinical deterioration following initiation of HAART and imaging showed contrast enhancement of the lesions. The symptoms regressed in four patients whereas the other four patients died. Neuropathological examination revealed severe inflammatory and demyelinating lesions with marked intraparenchymal and perivascular infiltration by macrophages and T lymphocytes. In some cases abundant viral proliferation was identified by immunocytochemistry or in situ hybridization, but in others the infectious agent could only be detected using PCR. T lymphocytes were predominantly CD8(+). In those cases with the more favorable course, inflammation was less severe with marked macrophage activation and a number of CD4(+) lymphocytes; in contrast, in the lethal cases inflammation was severe and mostly composed of CD8(+) cytotoxic lymphocytes. We conclude that HAART-induced paradoxical aggravation of HIV encephalitis or AIDS-related PML due to IRIS is reversible in most cases but may be lethal in others. In fatal cases, fulminant viral infection and/or acute perivenous leukoencephalitis may result from a dysregulation of the CD8(+)/CD4(+) T-cell balance.     

Influenza A virus and Reye's syndrome in adults.

We report fatal Reye's syndrome in two adults following proven influenza A viral infections. Reye's syndrome is, therefore, not confined to children but may also occur in adults. Many reported cases of postinfluenza A encephalopathy have clinical and pathological features of Reye's syndrome suggesting that they are not due to postinfectious perivenous demyelination.     

Gewinner der Globalisierung: Dengue-Viren und Japanisches Enzephalitisvirus – Erkrankungen in der Neurologie

Arboviruses are transmitted by arthropods, more than 100 of them are human pathogens and many of the arboviruses have neurotropic characteristics such as dengue viruses (DENV) and Japanese encephalitis virus (JE-V). Both DENV and JE-V belong to the genus Flavivirus. Climatic changes, food imports from the tropics and travel behavior have also increased the number of cases of diseases caused by tropical or subtropical viruses in Europe. Due to the close degree of relationship of the flaviviruses, coinfections with several arboviruses can occur. The DENV and JE-V are mosquito-borne infections caused by the genus Aedes spp. In cases of involvement of the central nervous system, the virus often reaches the brain via the blood-brain barrier. The DENV is a single-stranded RNA-positive virus with four known serotypes, DENV-1 to DENV-4. The DENV infections are usually asymptomatic and are known as classical dengue fever, the more severe courses are dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), usually with fatal outcome. Both DHF and DSS are classical second infections. A vaccination is not approved in Germany but has been approved for endemic regions since 2015. The course of an infection with JE-V initially runs characteristically and it is only characterized by encephalitis a few days later. For the JE-V a vaccine is approved even in Germany.     

Pathology, histochemistry and immunocytochemistry of lesions in acute multiple sclerosis

Twenty cases of acute or early multiple sclerosis have been examined using staining, histochemical or immunocytochemical methods. They had died within 6 months after initial clinical onset (12) or commencement of an "anatomically-remote" acute relapse (8). Plaques in these acute cases showed the following characteristics: lymphocytic perivascular infiltration, plaque hypercellularity, plaque macrophage infiltration and intra-macrophage myelin debris. In most cases of clinical duration of less than 12 weeks, some macrophages showed characteristic formaldehyde-resistant markers for haematogenous macrophages (muramidase, anti-alpha 11-antitrypsin, MAC and HAM56) but, with the exception of the last, these markers subsequently declined indicating a haematogenous origin for macrophages in the early lesion. Lymphocytes were prominent in perivascular (perivenous) regions but, except in one case, were only scanty in or at the demyelinating edge of plaques. Oligodendroglial hyperplasia, indicative of remyelinating activity, was seen at the edge of plaques in one quarter of these acute cases (7 times the rate seen in chronic lesions). Astrocytic activation was not apparent in the earliest stages but was usually seen from about 6 weeks onwards. The conclusion from these observations is that the prime inflammatory process is around blood vessels with usually only scanty initial inflammatory activity in the parenchyma of the brain. Macrophages emigrating from blood vessels digest myelin either as a response to inflammatory damage to the myelin or as a response to activation signals produced in either the perivascular region or plaque.     

Atypical ocular bobbing in acute organophosphate poisoning

Atypical ocular bobbing resulted from an intentional poisoning from dimpylate (Diazinon), an organophosphate compound. In discussing the possible foci and mechanism for atypical ocular bobbing associated with acute organophosphate poisoning, we suggest acetylcholine as a neurotransmitter substance within the ocular motor pathway. A literature review has not shown any previous reported cases with this sign.     

Magnetoencephalographic localization of epileptic foci using a 37-channel biomagnetometer]

The magnetoencephalography (MEG) and electroencephalography (EEG) were recorded simultaneously from 10 normal subjects using a 37-channel biomagnetometer. No paroxysmal spikelike waveform was observed in MEG at rest with eyes closed. The MEG and EEG were recorded also from 16 patients with primary epilepsy and 24 patients with secondary epilepsy. The examination proved to be safe for both normal subjects and patients with epilepsy. Interictal spikes were observed in 27 cases during the examination. The percentage of spikes identified in MEG but not in EEG was found to be 2. 3% of all spikes. The foci of the spikes identified in MEG were localized and determined in 20 cases. In 10 patients with secondary epilepsy, the localization of the foci were compared with the lesion demonstrated by magnetic resonance imaging (MRI) or computerized tomography (CT) and with the findings of EEG. In 6 cases, the foci by MEG were consistent. In the 4 cases where the MEG foci did not correspond to the MRI or CT findings, MEG foci were supported by the findings of EEG. MEG allows three-dimensional localization and enables us to elucidate the propagation of paroxysms. MEG was very useful in diagnosing epilepsy.     

MELAS with diffuse degeneration of the cerebral white matter: Report of an autopsy case

Up to now diffuse white matter demyelination of the cerebrum has been reported in only a few cases of mitochondrial encephalopathy with lactic acidosis and stroke‐like episodes (MELAS). Here we document an autopsy case with this rare neuropathology. Most MELAS cases are diagnosed antemortem by A3243G transition of mitochondrial DNA. While cerebral damage including necrotic foci in the cerebral cortex are common findings in MELAS, prominent white matter involvement best characterizes this MELAS case. There were numerous necrotic foci, varying in size and chronological stage, in the cerebral white matter. In the areas of the white matter without necrotic foci, there was diffuse fibrillary gliosis with the loss of axons and oligodendrocytes. The gliosis was dominant in the deep white matter, sparing the U‐fiber. The cerebral cortex showed diffuse cortical atrophy with few scattered necrotic foci. Distribution of the cerebral lesions does not coincide with the territory of blood supply. The vascular wall presented only slight to mild hyalinosis. We assumed a common pathogenesis to the cortical lesions and the white matter change. The pathogenesis of the present diffuse cerebral lesions may not be just secondary to circulatory disturbance but partly due to metabolic abnormality.     

Alpha-1-antichymotrypsin in human glioblastoma multiforme cells and its relation to GFAP immunostaining.

Biopsies of 20 different patients with glioblastoma multiforme were treated with 0.1% protease and stained for alpha-1-ACT. Simultaneous glial fibrillary acidic protein (GFAP) staining of mirror sections was performed. In four cases no neoplastic cells were stained with alpha-1-ACT. The other 11 cases displayed minute accumulations of immunostained neoplastic cells in spongiotic foci. Some scattered immunostained cells not differentiable from neoplastic cells were noticed. Staining of neoplastic as well as branched intratumoral astrocytes for alpha-1-ACT and GFAP of equal distribution and intensity was detected in one case. The alpha-1-ACT immunostaining of peritumoral reactive astrocytes has been observed in 8 cases, 7 of them, however with a smaller amount of cells, entirely corresponding to the distribution and intensity of GFAP. This might represent the absorption of antigen by degenerating cells.     

Activation of the epileptic focus by transcranial magnetic stimulation of the human brain

To establish whether transcranial magnetic stimulation is able to activate the primary epileptic focus preferentially, 13 patients who had medically intractable complex partial seizures were examined prior to surgical therapy. Single or a series of magnetic stimuli were applied to various regions of the skull. The effects of transcranial magnetic stimulation were monitored via subdurally implanted electrodes. In the process of presurgical evaluation, the dosage of anticonvulsant medication had been reduced in all patients but one. Transcranial magnetic stimulation was able to activate the epileptic focus (or foci) in 12 of the 13 patients. Distinct patterns of focal activation were observed in 3 patients who had several foci. No epileptiform potentials were induced outside epileptic foci, which had been identified by corticographic recordings. In one patient a complex partial seizure that was induced was identical to her habitual seizures. In another patient, a complete transition from a nonactive theta focus to a self-sustained epileptic focus occurred. A facilitation of epileptiform afterdischarge was seen with sequential stimulation. No adverse effects were either reported by the patients or observed by the investigators. In summary transcranial magnetic stimulation is able to activate the epileptic focus (or foci) and consequently may be an additional tool for the localization of epileptic foci in presurgical evaluation.     

Neurological complications of dengue fever: Experience from a tertiary center of north India

Introduction:

Dengue, an acute viral disease transmitted by Aedes mosquitoes, is highly endemic in many tropical and subtropical areas of the world. Neurological complications of dengue infection have been observed more frequently in the recent past and some studies highlighted varied neurological complications arising in the course of dengue illness. In this retrospective study, we report various neurological complications observed during the last 2 years in patients of dengue fever.

Materials and Methods:

The patients presenting with neurological complications with positive serology (IgM antibody) for dengue infection were consecutively recruited from the Department of Neurology/Medicine from a tertiary center of Lucknow, India. These patients were subjected to a detailed clinical evaluation, laboratory assessment including blood count, hematocrit, coagulation parameters, biochemical assays, serology for dengue fever, enzyme-linked immunosorbent assay for human immunodeficiency virus and other relevant investigations.

Results:

Twenty-six patients with neurological complications associated with confirmed dengue infection were observed during the last 2 years. Eighteen of these patients were male. Of the 26 patients, 10 patients were suffering from brachial neuritis, four patients had encephalopathy, three patients were consistent with the diagnosis of Guillain Barre syndrome, three patients had hypokalemic paralysis associated with dengue fever and two patients had acute viral myositis. Opsoclonus-myoclonus syndrome was diagnosed in two patients, myelitis in one patient and acute disseminated encephalo-myelitis also in one patient.

Conclusion:

Dengue fever was associated with widespread neurological complications. Brachial neuritis and opsoclonus-myoclonus syndrome were observed for the first time in this study.     

Systematic EEG follow-up study of traumatic psychosis

Summary A systematic 2 year follow-up study of EEG in 100 patients suffering from traumatic psychosis with amnesia lasting more than 1 week led to the following results. (1) EEG foci were demonstrated in 95% of cases, and bilaterally in 70%. Normalization occurred within 3 months in 48% of patients, with foci persisting for more than 2 years in 22% mostly in patients with traumatic epilepsy. Focal signs initially consisted of delta foci (85%) and finally of focal dysrhythmia (72%), with temporal localization increasing from 58% to 82%. EEG foci were associated with neurological focal symptoms in 49% of cases and skull fractures in 78%. (2) During psychosis a general slowing of EEG was constantly observed. Normalization occurred within 3 months in 28% of patients. Rarely slowing lasted longer than 6 months. (3) It took longer to normalize general slowing than EEG foci, but slowing disappeared more completely. The left predponderance of EEG foci in traumatic psychosis could not be confirmed, the hypothesis of a pathoplastic role of the speech dominant hemisphere was not proved.     

Brain involvement in Dengue fever.

During the 1994-1995 outbreak of dengue fever in New Caledonia (1079 cases), two cases of encephalopathy were seen. Both patients suffered transient clinical (drowsiness, confusion) and electroencephalographic disturbances from which they fully recovered. Although this condition has been described in dengue infection a number of different pathological mechanisms are probably implicated.     

A rapid immunohistochemical test to distinguish congenital myotonic dystrophy from X-linked myotubular myopathy

Severe forms of myotubular myopathy (MTM) and congenital myotonic dystrophy type 1 (CDM), both present as floppy infants with hypotonia, respiratory failure and bulbar insufficiency. Muscle biopsy is often performed as part of the diagnostic process, but these two disorders share very similar histopathological features. It is well documented that CDM muscle has nuclear foci that contain muscleblind-like 1 (MBNL1) protein. In muscle biopsies from eight neonates showing central nuclei, MBNL1 immunolocalisation identified discrete, intensely stained foci in three cases that were subsequently confirmed as CDM by DNA analysis. In the five remaining non-CDM patients and two controls, MBNL1 staining was heterogeneous in nuclei, not as foci. MBNL1 staining patterns in CDM were easily distinguishable from MTM. We suggest that in cases of hypotonia with suspected CDM or MTM, when biopsy has been taken, sections should additionally be stained for MBNL1 to provide a rapid indication of a CDM diagnosis.     

Papillophlebitis: Benign retinopathy resembling papilledema or papillitis

Three young adult patients are described to illustrate an uncommon syndrome, papillophlebitis. This entity, characterized by mild but protracted monocular visual impairment, edema of the optic disc, retinal venous engorgement, and perivenous retinal hemorrhages, resembles atherosclerotic occlusion of the central retinal vein in older patients. In younger individuals it is benign and self limited, but may be incorrectly diagnosed as optic neuritis or papilledema. These alternatives can usually be excluded if tests of visual function do not indicate an optic nerve conduction defect and if the clinical presentation and examination of the opposite ocular fundus do not disclose evidence of increased intracranial pressure. Because resolution usually occurs spontaneously, immediate neuroroenotenographic tests may be inappropriate. Effective treatment has not been established; local instillation of corticosteroids may hasten recovery.     

Childhood epilepsy uncontrolled by phenytoin: clinical and electroencephalographic study.

Nine cases of childhood epilepsy manifesting motor convulsions uncontrolled despite high levels of phenytoin (PHT) were studied clinically and electroencephalographically. These cases consisted of five cases of partial seizures without impairment of consciousness, two cases of partial seizures (occasionally generalized seizures beginning locally), one case of predominantly unilateral seizures, and one case of generalized tonic-clonic seizures. the onset of seizures was at a rather early age, between 3 months and 9 years, and under 3 years of age in eight cases. All cases had single or multiple, cortical epileptic foci in EEG. The projection of spikes was localized to a rather limited area. Seizures of these patients were frequent. All cases, except one, did not respond to other medication. Convulsive seizures with cortical focal spike foci in EEG uncontrolled despite high levels of PHT were thought to have poor responsiveness to not only PHT itself, but also to other anticonvulsants.     

An Autopsied Case of Acute Hemorrhagic Leukoencephalitis

Abstract: This is a clinico-pathological study of one case of acute hemorrhagic leukoencephalitis occurring in a patient with lung cancer. The main changes observed by light microscopywere in the white matter. All of these changes were the result of hemorrhage and demyelination around the venous vessels. Glial mesenchymal reactions were minimal. In view of these findings, this case supports the hypothesis that immune mechanisms play a role in the pathogenesis of neuropsychiatric symptoms during malignant illnesses. Here we will discuss the problem of differential diagnoses of acute hemorrhagic leukoencephalitis and its close morphologic similarities to perivenous encephalitis. Acute hemorrhagic leukoencephalitis and perivenous encephalitis may be a single entity of a demyelinating disease.